Epidemiological transcriptomic data supports BCG protection in viral diseases including COVID-19

Epidemiological evidence suggests that Bacille Calmette-Guerin (BCG) vaccine induced trained immunity protects against non-specific infections including coronavirus disease 2019 (COVID-19). A recent clinical trial has also supported BCG protection in viral respiratory infections in general, with multiple COVID-19 specific trials currently ongoing. The durability and mechanism of BCG trained immunity however remain unclear. An integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and viral respiratory infections, along with transcriptomic alterations reported in COVID-19, is presented here toward addressing this gap. Results show that BCG vaccination leads to a very long-lasting transcriptomic changes which mimic viral infections by upregulated antiviral defense response, and oppose viral infections by downregulated myeloid cell activation mediated immune response. Antiviral defense upregulation is consistent with the present concept of trained immunity, whereas downregulation of myeloid cell activation seems directionally inconsistent, with enhancement of innate immune response considered to characterize trained immunity. The present finding is however in consonance with recent retrospective cohort study and clinical trial evidence that shows no association of BCG vaccination with systemic inflammation, alleviating the concern that the vaccine may add to inflammatory response and worsen severe COVID-19. In conclusion, the present analysis offers transcriptomic support to the existing epidemiological evidence of lower prevalence and mortality of COVID-19 in countries with childhood BCG vaccination policy.